Tuberculosis (TB) is the leading cause of death in people with HIV infection and is prevalent in clinical settings where HIV care is provided. Among pregnant women with HIV infection, TB is an important cause of maternal morbidity and mortality, and may be associated with increased mother-to-child transmission (MTCT) of HIV and excess infant mortality. We have found that 2-3% of HIV-infected pregnant women in Soweto, South Africa, have previously undetected TB, increasing the risk of adverse outcomes for them and their offspring. Moreover, treatment of TB during pregnancy has the potential to interfere with the efficacy of treatment to prevent MTCT with the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz because of upregulation of P450 cytochromes by rifampin, the key drug in TB therapy. The goal of this proposal is to study the impact of TB/HIV co-infection in pregnancy on maternal and infant outcomes, and to characterize the impact of TB treatment using rifampin on the pharmacokinetics and pharmacodynamics of NNRTIs used for prevention of MTCT. We will assemble a prospective cohort of 250 HIV- and TB-infected pregnant women recruited from antenatal clinics in Soweto and the obstetrics ward at the Chris Hani Baragwanath Hospital and 500 HIV-infected pregnant women without TB matched based on gestational age and site of enrollment. Participants will undergo baseline clinical and laboratory evaluations and will be followed through pregnancy, labor and delivery and 6 months post-partum to record maternal and infant HIV, TB and overall outcomes. We will determine the association of TB and maternal CD4 counts and HIV viral loads, HIV-related complications and deaths, and transmission of HIV to infants. We will also assess the impact of TB on obstetric and infant outcomes, including prematurity, low birth weight, post-partum infections and survival. Additionally, we will conduct pharmacokinetic sampling over 48 hours after the onset of labor and use pharmacokinetic modeling to determine the impact of concomitant rifampin use on NNRTI exposure and efficacy during pregnancy and the peripartum period. This study will yield extremely important data on the outcomes of TB and its treatment in HIV- infected, pregnant women that will be widely applicable in Africa and other regions where women and infants are threatened by this deadly co-infection.